Hepatic lipase (LIPC) sequencing in individuals with extremely high and low high-density lipoprotein cholesterol levels

PLoS One. 2020 Dec 16;15(12):e0243919. doi: 10.1371/journal.pone.0243919. eCollection 2020.


Common variants in the hepatic lipase (LIPC) gene have been shown to be associated with plasma lipid levels; however, the distribution and functional features of rare and regulatory LIPC variants contributing to the extreme lipid phenotypes are not well known. This study was aimed to catalogue LIPC variants by resequencing the entire LIPC gene in 95 non-Hispanic Whites (NHWs) and 95 African blacks (ABs) with extreme HDL-C levels followed by in silico functional analyses. A total of 412 variants, including 43 novel variants were identified; 56 were unique to NHWs and 234 were unique to ABs. Seventy-eight variants in NHWs and 89 variants in ABs were present either in high HDL-C group or low HDL-C group. Two non-synonymous variants (p.S289F, p.T405M), found in NHWs with high HDL-C group were predicted to have damaging effect on LIPC protein by SIFT, MT2 and PP2. We also found several non-coding variants that possibly reside in the circRNA and lncRNA binding sites and may have regulatory potential, as identified in rSNPbase and RegulomeDB databases. Our results shed light on the regulatory nature of rare and non-coding LIPC variants as well as suggest their important contributions in affecting the extreme HDL-C phenotypes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • African Americans
  • Alleles
  • Binding Sites / genetics
  • Cholesterol / blood
  • Cholesterol / genetics
  • Cholesterol Ester Transfer Proteins / blood
  • Cholesterol Ester Transfer Proteins / genetics
  • Cholesterol, HDL / blood*
  • Cholesterol, HDL / genetics
  • Cholesterol, LDL / blood*
  • Cholesterol, LDL / genetics
  • European Continental Ancestry Group
  • Female
  • Genotype
  • Humans
  • Introns / genetics
  • Lipase / genetics*
  • Lipase / ultrastructure
  • Lipid Metabolism / genetics
  • Lipids / blood
  • Lipids / genetics
  • Male
  • Polymorphism, Single Nucleotide
  • Protein Binding / genetics
  • Protein Conformation
  • RNA, Circular / blood
  • RNA, Circular / genetics
  • RNA, Long Noncoding / genetics
  • Triglycerides / blood
  • Triglycerides / genetics


  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Cholesterol, LDL
  • LIPC protein, human
  • Lipids
  • RNA, Circular
  • RNA, Long Noncoding
  • Triglycerides
  • Cholesterol
  • Lipase

Grant support

This study was supported by the National Heart, Lung and Blood Institute (NHLBI) grant, HL084613 (M. Ilyas Kamboh). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.